UFT is an oral anticancer agent comprised of tegafur and uracil at a molar ratio of 1 to 4 which has good absorption in the small intestine. (Fujii, S., et al., 1979; U.S. Pat. No. 4,328,229). Tegafur is gradually converted to 5-fluorouracil via the metabolism of liver enzyme P450. Uracil enhances the serum 5-fluorouracil concentration by the competitive inhibition of dihydropyrimidine dehydrogenase, the enzyme responsible for 5-fluorouracil catabolism. (Ikenaka, K., et al., 1979). Oral UFT administration reportedly generates a higher maximum plasma level of 5-fluorouracil than the protracted intravenous injection of 5-flourouracil given in a dose equimolar to the tegafur in UFT. (Ho, D. H., et al., 1998).
The response rate of single UFT treatments in patients with advanced stage lung cancer is reported to be 6 to 8 percent. (Shimizu, E., et al., 1986; Keicho, N., et al., 1986). Combination chemotherapy consisting of a daily administration of UFT for two or three weeks, and a bolus injection of cisplatin in advanced non-small cell lung cancer patients yields a response rate of 29 percent to 38 percent and a median survival time of eight to thirteen months. (Ichonose, Y., et al., 1995; Ichinose, Y., et al., 2000; Saito, J., et al., 2001). In two trials for locally advanced non-small cell lung cancer patients, the combination chemotherapy of UFT plus cisplatin with concurrent radiotherapy shows a response rate of 80 percent (Ichinose, Y., et al., 2002) and 94 percent (Ichinose, Y., et al., 1999) and a median survival rate of 16.5 months. (Ichinose, Y., et al., 2002). These results of UFT plus cisplatin chemotherapy regimens are comparable to those of other recently published cisplatin based doublet chemotherapy regimens. (Schiller, J. H., et al., 2002; Vokes, E. E., et al., 2002).
Adenocarcinoma, a form of non-small cell lung cancer (NSCLC), accounts for approximately 40% of all cases of lung cancer. It is the most common form of NSCLC and the most common type of lung cancer overall.
Concerning adjuvant treatment using UFT, the West Japan Study Group for Lung Cancer Surgery reported that postoperative adjuvant treatment with UFT (400 mg/day for 1 year) in patients with completely resected stage I-III disease prolonged survival significantly longer than observation alone. (Wada, H., et al., 1996). The 5-year survival rate was 64 percent in the UFT group and 49 percent in the control group (P=0.02). In a subgroup analysis, no statistically significant difference in the overall survival of patients with squamous cell carcinoma between the two groups was observed (P=0.24). In contrast, for the patients with adenocarcinoma in the UFT group, most of whom had stage I disease, survival was significantly better than for those in the control group (P=0.009). (Okimoto, N., et al., 1996).
Improved methods for extending survival while causing minimal side effects in postoperative lung cancer patients, particularly in patients with adenocarcinoma, are needed.